The overall goal of this Program Project Grant (P01) is to defne the key interactions between multiple intracellular pathogens and infected host cells. Over the last 10 years, many of the host innate immune pathways involved in sensing microbial infection have been identified. The receptors controlling the activation of these pathways include the Toll-like receptors (TLRs) and a growing family of cytosolic receptors including Nods, Naips, Nalps, and multiple cytosolic nucleic acid sensors (collectively termed NLRs). Importantly, the contribution of each of these pathways during a microbial infection will differ based on the composition, lifestyle, and virulence mechanisms of that microbe. Core C of this P01 will maintain a colony of mouse strains with deficiencies in components of innate immunity. These mice and macrophages derived from these mice will be distributed to each of the projects within the P01. In Aim 1 we will acquire these mouse strains and ensure that they have all been backcrossed onto the C57BI/6 genetic background to equivalent degrees. In Aim 2 we will intercross certain strains to generate mice deficient in multiple components of innate immunity. In Aim 3 we will cryopreserve macrophages derived from each of the mouse strains maintained in Aims 1 and 2. These macrophages and mice will be distributed to each of the P01 labs as necessary. Core C will reduce overall mouse costs due to economies of scale. In addition, each P01 project will benefit from using cells and mice with fewer genetic and experimental variations.